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HNF1B基因内的一种常见变异与多发性骨髓瘤患者的总生存期相关:来自IMMEnSE联盟的结果及荟萃分析。

A common variant within the HNF1B gene is associated with overall survival of multiple myeloma patients: results from the IMMEnSE consortium and meta-analysis.

作者信息

Ríos-Tamayo Rafael, Lupiañez Carmen Belén, Campa Daniele, Hielscher Thomas, Weinhold Niels, Martínez-López Joaquin, Jerez Andrés, Landi Stefano, Jamroziak Krzysztof, Dumontet Charles, Wątek Marzena, Lesueur Fabienne, Reis Rui Manuel, Marques Herlander, Jurczyszyn Artur, Vogel Ulla, Buda Gabriele, García-Sanz Ramón, Orciuolo Enrico, Petrini Mario, Vangsted Annette J, Gemignani Federica, Försti Asta, Goldschmidt Hartmut, Hemminki Kari, Canzian Federico, Jurado Manuel, Sainz Juan

机构信息

Genomic Oncology Area, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain.

Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain.

出版信息

Oncotarget. 2016 Sep 13;7(37):59029-59048. doi: 10.18632/oncotarget.10665.

Abstract

Diabetogenic single nucleotide polymorphisms (SNPs) have recently been associated with multiple myeloma (MM) risk but their impact on overall survival (OS) of MM patients has not been analysed yet. In order to investigate the impact of 58 GWAS-identified variants for type 2 diabetes (T2D) on OS of patients with MM, we analysed genotyping data of 936 MM patients collected by the International Multiple Myeloma rESEarch (IMMENSE) consortium and an independent set of 700 MM patients recruited by the University Clinic of Heidelberg. A meta-analysis of the cox regression results of the two sets showed that rs7501939 located in the HNF1B gene negatively impacted OS (HRRec= 1.44, 95% CI = 1.18-1.76, P = 0.0001). The meta-analysis also showed a noteworthy gender-specific association of the SLC30A8rs13266634 SNP with OS. The presence of each additional copy of the minor allele at rs13266634 was associated with poor OS in men whereas no association was seen in women (HRMen-Add = 1.32, 95% CI 1.13-1.54, P = 0.0003). In conclusion, these data suggest that the HNF1Brs7501939 SNP confers poor OS in patients with MM and that a SNP in SLC30A8 affect OS in men.

摘要

致糖尿病的单核苷酸多态性(SNPs)最近被认为与多发性骨髓瘤(MM)风险相关,但它们对MM患者总生存期(OS)的影响尚未得到分析。为了研究58个经全基因组关联研究(GWAS)鉴定的2型糖尿病(T2D)相关变异对MM患者OS的影响,我们分析了国际多发性骨髓瘤研究(IMMENSE)联盟收集的936例MM患者以及海德堡大学诊所招募的700例MM患者的独立队列的基因分型数据。对这两组数据的cox回归结果进行荟萃分析显示,位于HNF1B基因的rs7501939对OS有负面影响(HRRec = 1.44,95%CI = 1.18 - 1.76,P = 0.0001)。荟萃分析还显示,SLC30A8基因的rs13266634 SNP与OS存在值得注意的性别特异性关联。rs13266634位点每多一个次要等位基因拷贝,男性的OS就较差,而女性则无此关联(HRMen-Add = 1.32,95%CI 1.13 - 1.54,P = 0.0003)。总之,这些数据表明,HNF1B基因的rs7501939 SNP会导致MM患者的OS较差,而SLC30A8基因的一个SNP对男性的OS有影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aba9/5312293/47711d695fb9/oncotarget-07-59029-g001.jpg

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